Toxicities of cancer immunotherapy: clinical manifestations, underlying mechanisms, and management

Abstract

Abstract Cancer immunotherapy, particularly immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T-cell (CAR-T) therapy, has transformed the treatment landscape of multiple malignancies. However, dysregulated immune activation can cause a wide range of toxicities that may disrupt treatment, impair long-term health, and reduce quality of life. This review summarizes the clinical manifestations, underlying mechanisms, long-term consequences, and management of toxicities associated with ICIs and CAR-T-cell therapy. It covers immune-related adverse events induced by ICIs; cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, which occur predominantly after CAR-T-cell therapy; and hematologic and organ-specific toxicities affecting the skin, gastrointestinal tract, liver, lungs, heart, kidneys, endocrine organs, and nervous system. Late-onset and persistent complications, including fatigue, endocrine dysfunction, gastrointestinal disorders, neurological impairment, and psychological distress, are also discussed. These toxicities may result from excessive immune activation, loss of immune tolerance, cytokine dysregulation, alterations in the tumor microenvironment, treatment interactions, and individual susceptibility. Early recognition, close monitoring, standardized toxicity grading, and individualized management are essential to minimize severe complications while preserving antitumor efficacy. Future studies should focus on identifying reliable predictive biomarkers and developing risk-stratification models to improve the safety and personalization of cancer immunotherapy.